Lecture 23 Dr VDH

Protective strategies of the oral mucosa

Stratified squamous epithelial cells provide a multilayered barrier that resists microbial penetration and mechanical stress.

Function of keratinized oral mucosa

Keratinized regions (gingiva and hard palate) resist friction and bacterial invasion during mastication.

Role of epithelial tight junctions

Prevent penetration of pathogens and toxins through intercellular spaces.

Antimicrobial peptides produced by oral epithelium

Defensins and histatins that disrupt microbial membranes and kill pathogens.

Function of defensins

Small cationic peptides that form pores in microbial membranes, causing cell death.

Function of histatins

Salivary peptides with antimicrobial properties that destabilize microbial membranes.

Significance of the gingival crevice

A vulnerable area where thin junctional epithelium is exposed to microbial biofilm.

Function of junctional epithelium

Allows passage of immune cells and gingival crevicular fluid; acts as a frontline defense interface with plaque biofilm.

Role of immune cells in the junctional epithelium

Neutrophils migrate continuously through the tissue to patrol and neutralize microbes.

Definition of gingival crevicular fluid

A serum-like exudate flowing through the junctional epithelium into the gingival sulcus.

Contents of GCF

Plasma proteins, cytokines, complement, immunoglobulins, and immune cells like neutrophils and macrophages.

Clinical significance of GCF

Its composition reflects the inflammatory status of the adjacent gingiva.

Role of GCF in defense

Flushes microbes and delivers host defense molecules to the sulcus.

Major antimicrobial proteins in saliva

Lactoferrin, lysozyme, histatins, defensins, mucins, and secretory immunoglobulin A (sIgA).

Function of lactoferrin

Binds iron to limit bacterial growth and inhibits viral replication.

Function of lysozyme

Breaks bacterial cell walls by hydrolyzing peptidoglycan bonds.

Function of mucins

Trap and aggregate microbes while forming a protective physical barrier.

Function of secretory IgA

Agglutinates bacteria, neutralizes toxins, and prevents microbial adherence to mucosal surfaces.

Role of cytokines in saliva

Mediate local immune responses and signal immune cell activation.

Immune cells found in saliva

Neutrophils, monocytes, lymphocytes, and dendritic cells that participate in defense.

Definition of acquired enamel pellicle

A thin proteinaceous layer derived from saliva that coats enamel surfaces.

Function of the enamel pellicle

Acts as a semipermeable barrier that buffers acids and slows demineralization.

Pellicle lubrication role

Provides a smooth surface to reduce friction from mastication and toothbrushing.

Selective adsorption in pellicle

Binds beneficial salivary proteins like statherin and proline-rich proteins that stabilize minerals.

Pellicle's role in bacterial adhesion

Favors attachment of commensals over pathogenic bacteria.

Role of commensal microorganisms

Compete with pathogens for nutrients and space while promoting immune tolerance.

Purpose of innate immunity in the oral cavity

Provides rapid, nonspecific defense through barriers, antimicrobial molecules, and immune cells.

Role of toll-like receptors (TLRs)

Recognize pathogen-associated molecular patterns (PAMPs) and activate cytokine-mediated inflammation.

Effect of TLR activation

Triggers signaling cascades that lead to cytokine release and immune cell activation.

Key inflammatory mediators in periodontium

Cytokines (IL-1β, IL-6, IL-17, TNF-α), chemokines, and prostaglandins (PGE2).

Function of cytokines

Regulate inflammation, recruit immune cells, and activate osteoclasts to promote bone resorption.

Function of chemokines

Act as chemoattractants that guide neutrophils and macrophages to infection sites.

Function of prostaglandins (PGE2)

Stimulate bone resorption, vasodilation, and pain; blocked by NSAIDs to reduce bone loss.

Neutrophil functions

Phagocytose pathogens, release defensins and lysozyme, produce ROS, and form neutrophil extracellular traps (NETs).

Macrophage functions

Remove debris, secrete MMPs and cytokines, and contribute to tissue remodeling and inflammation.

Mast cell functions

Release nitric oxide, matrix metalloproteinases, and TNF-α to amplify inflammation.

Dendritic cell functions

Capture and degrade antigens, migrate to lymph nodes, and present antigens to T cells.

Natural killer (NK) cell function

Recognize and kill virus-infected or tumor cells and promote dendritic cell maturation.

Function of matrix metalloproteinases (MMPs)

Degrade extracellular matrix components such as collagen and elastin.

Regulation of MMP activity

Balanced by tissue inhibitors of metalloproteinases (TIMPs); imbalance causes tissue destruction.

Function of the complement system

Opsonizes pathogens, enhances inflammation, and lyses microbes via the membrane attack complex.

Complement activation pathways

Classical (antibody-mediated), alternative (pathogen surface), and lectin (mannose-binding).

Central complement molecule C3

Produces C5 convertase, opsonizes bacteria, and triggers cell lysis.

Components of adaptive immunity

T lymphocytes and B lymphocytes that provide specific, long-term immune responses.

Function of MHC class I molecules

Present endogenous antigens to CD8+ cytotoxic T cells to kill infected cells.

Function of MHC class II molecules

Present exogenous antigens to CD4+ helper T cells to activate adaptive immunity.

Helper T cell (CD4+) function

Secrete cytokines that coordinate immune cells and promote B cell antibody production.

Cytotoxic T cell (CD8+) function

Directly destroy virus-infected or damaged host cells.

Regulatory T cell (Treg) function

Suppress excessive immune reactions to maintain immune tolerance.

Th17 cell function

Secrete IL-17 to promote inflammation, RANKL expression, and bone resorption.

Role of B lymphocytes

Differentiate into plasma cells that produce antibodies and memory B cells for future responses.

Protective role of B cells

Produce antibodies that neutralize pathogens and prevent dysbiosis.

Destructive role of B cells in periodontitis

Secrete IL-1, IL-6, TNF-α, MMPs, and RANKL that promote bone resorption.

Main cell types in bone remodeling

Osteoblasts (form bone), osteocytes (maintain matrix), and osteoclasts (resorb bone).

Cytokines that stimulate bone resorption

IL-1β, IL-6, IL-17, TNF-α, and prostaglandin E2.

Function of the RANKL-RANK-OPG system

RANKL binds RANK to activate osteoclasts; OPG inhibits this interaction to prevent bone loss.

RANKL/OPG imbalance in periodontitis

Increased RANKL and decreased OPG promote osteoclast activation and alveolar bone resorption.

Initial lesion of periodontitis (2-4 days)

Subclinical inflammation with PMN infiltration, vasodilation, and early collagen loss.

Early lesion (4-7 days)

Lymphocyte and macrophage infiltration, cytokine release, and localized inflammation.

Established lesion (2-3 weeks)

Plasma cell predominance, antibody and complement presence, epithelial migration, and tissue breakdown.

Advanced lesion (3+ weeks)

Clinical periodontitis with pocket formation, alveolar bone loss, and chronic inflammation.

How dysbiosis triggers immune response

Pathogenic biofilm activates TLRs leading to cytokine release and recruitment of neutrophils and macrophages.

Role of fibroblasts in periodontal inflammation

Produce cytokines and MMPs that perpetuate inflammation and connective tissue breakdown.

T cell contribution to bone loss

Th17 and other T cells secrete IL-17 and RANKL to promote osteoclast activity.

Key immune cells in dental pulp

Odontoblasts, fibroblasts, neutrophils, macrophages, dendritic cells, T and B cells, NK cells, and mast cells.

Odontoblast function in pulp immunity

Detect pathogens via toll-like receptors and secrete cytokines to recruit immune cells.

Major mediators in pulpal inflammation

Cytokines (IL-1β, TNF-α), chemokines (IL-8, CCL2), prostaglandins, and complement proteins.

Acute pulp inflammation

Characterized by vasodilation, increased permeability, and neutrophil recruitment.

Chronic pulp inflammation

Dominated by macrophages, T and B cells, plasma cells, leading to fibrosis or granuloma formation.

Overall protective systems in the oral cavity

Include epithelial barriers, saliva, GCF, pellicle, commensal microbes, and immune cells maintaining homeostasis.

Result of immune imbalance in oral cavity

Dysbiosis and chronic inflammation lead to tissue destruction and bone loss in periodontitis and pulpitis.